MicroRNAs in Kidney Development

描述（由申请人提供）：肾脏发育中的微小RNA微小RNA（miRNA）是在转录后水平调节基因表达的小的非编码RNA分子。近年来，在多种多细胞生物中发现了数百种miRNAs，其中许多miRNAs在进化上是保守的。尽管大多数miRNAs的生物学功能仍然未知，但它们被预测广泛调节基因翻译和mRNA稳定性。此外，最近的研究表明miRNA与癌症形成有关，并表明miRNA水平的变化可能具有微妙的致病缺陷。在这项资助提案中，我们将测试miRNAs在功能性肾脏发育中的关键作用这一假设。关于miRNAs和肾脏发育的信息很少。因此，我们建议首先使用原位杂交技术对小鼠肾脏不同发育阶段所有已鉴定的miRNA的表达谱进行分类。其次，通过比较这些肾特异性miRNA在小鼠中的表达与它们在非洲爪蟾的原肾中的对应物的表达来鉴定进化上保守的miRNA。最后，通过从非洲爪蟾胚胎中消除miRNA生物发生的关键组分Dicer，将直接测试miRNA在肾脏发育中的潜在作用。然后将使用一组肾脏特异性标记基因、组织学和生理学研究来研究对原肾发育和近端-远端模式的影响。这一建议将为今后研究小鼠肾脏发育过程中的单个miRNAs提供基础。此外，从小鼠肾脏获得一套完整的miRNA表达数据将对社区非常有帮助。例如，它将有助于快速有效地分析各种肾脏疾病小鼠模型中的miRNA。该项目旨在研究一种非编码小RNA（microRNA）在肾脏发育中的作用。microRNA已被证明参与许多疾病过程，包括神经系统疾病如图雷特综合征、癌症形成和病毒如疱疹病毒的传播。肾脏中microRNA的鉴定和表征将为解决microRNA是否也在某些肾脏疾病中发挥作用提供一个起点。

DESCRIPTION (provided by applicant): MicroRNAs in Kidney Development MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level. In recent years, hundreds of miRNAs have been identified in various multicellular organisms and many of the miRNAs are evolutionarily conserved. Although the biological functions of most miRNAs are still unknown, they are predicted to broadly regulate gene translation and mRNA stability. In addition, recent studies implicate miRNAs in cancer formation and suggest that changes in miRNA levels can have subtle disease-causing defects. In this grant proposal, we will test the hypothesis that miRNAs are crucial players in the development of a functional kidney. Very little information is available about miRNAs and kidney development. Therefore, we propose first to catalogue the expression profile of all identified miRNAs in the mouse kidney at different stages of development using in situ hybridization. Secondly, evolutionarily conserved miRNAs will be identified by comparing the expression of these kidney-specific miRNAs in mouse to the expression of their counterparts in the pronephric kidney of Xenopus. Finally, a potential role for miRNAs in kidney development will be tested directly by eliminating the key component of miRNA biogenesis, Dicer, from Xenopus embryos. The effect on development and proximal-distal patterning of the pronephros will then be studied using a panel of kidney-specific marker genes, histology and physiological studies. This proposal will provide the basis for future studies of individual miRNAs during mouse kidney development. In addition, the availability of a complete set of miRNA expression data from the mouse kidney will be extremely helpful for the community. It will - for example - facilitate a fast and efficient analysis of miRNAs in various mouse models of kidney diseases. This project addresses the role of a species of non-coding small RNAs (microRNAs) in kidney development. microRNAs have been shown to be involved in many disease processes including neurological disorders such as Tourette's syndrome, cancer formation and the propagation of virus such as Herpes Virus. The identification and characterization of microRNAs in the kidney will provide a starting point to address whether microRNAs also play a role in some of the kidney diseases.